Non-visual Impacts of Light on Effective Connectivity associated to executive brain responses

Abstract

peer reviewedIntroduction: Beyond vision, light have many non-visual biological effect including the stimulation of alertness and cognition. These effect are considered to be mediated mainly through the recently discovered blue-light-sensitive intrinsically photosensitive retinal ganglion cells i.e. ipRGCs (Warthen, D. M., & Provencio, 2012)⁠⁠⁠ Direct projections of ipRGCs mainly reach subcortical structures, including the hypothalamus and thalamus. However, non-visual impact of light have also been reported on the activity of cortical regions, presumably through an initial subcortical impact. Here, we assessed the impact of blue-enriched light on the connectivity of a brain network sustained the brain activity associated with an ongoing auditory executive task in healthy young adults. We anticipated that blue-enriched light would mainly affect subcortical to cortical connectivity. Method: 20 healthy participants (60% Female, 23.2±4.1 years) who met our inclusion criteria assessing both physical and mental health in addition to having regular sleep habits, were included in the study. Participants started the study protocol by a structural 7T MRI scan in which high resolution T1-weighted structural images of their brain were collected. Following a loose sleep-wake schedule (±1.5h; verified with actigraphy) for 7 days, participants came to the lab, ~2 hours before/after their habitual sleep/wake time to do a functional 7T MRI scan (GRE-EPI sequence, TR = 2340 ms, TE = 24 ms, voxel size = 1.4 × 1.4 × 1.4 mm3). Participant completed an auditory working memory task (N-back: 0-back and 2-back) under different light conditions including an active blue-enriched polychromatic light, to stimulate ipRGCs (6500K; 190, 92 and 37 melanopic Equivalent Daylight Illumination (EDI) lux) and a control monochromatic orange light (590nm; 0.2 mel EDI luc), to which ipRGCs are almost nonresponsive. Based on a standard whole-brain GLM analyses using SPM12, 3 regions significantly involved in the N-back task (p FWE whole-brain < 0.05) were isolated: a dorsoposterior part of the thalamus corresponding to the pulvinar, the Intraparietal sulcus (IPS) and Anterior insula (AI) (Figure.1) Effective connectivity among the 3 region network and the modulatory effect of different light conditions on the inter-region connections were estimated using the Dynamic Causal Modeling as part of SPM12 (Figure.2A). Effects were considered robust for posterior probably (Pp) > .95. Results: The DCM analysis indicated that only the driving inputs of the 2-back task was effective for the IPS and AI) (Pp ≥ .95). The baseline effective connectivity showed that among the connections defined in the initial model, 3 connections were robust (Pp ≥ .95). The pulvinar to IPS and pulvinar to AI connectivity were excitatory while the AI to IPS connectivity was inhibitory (Figure.2B). Evaluation of the modulatory effect of light conditions (blue-enriched and orange) revealed a significant modulation of the connections going from the pulvinar to both the IPS and AI with only blue-enriched light was significantly strengthening the two aforementioned connectivity (Pp ≥ .95) (Figure.2C). Conclusion: These results are in line with an initial impact of non-visual light on the information flow going from subcortical to cortical areas(Vandewalle et al., 2005)⁠. In the context of an executive task, blue-enriched, but not orange light, seems to affect thalamo-cortical loops. Future analyses will considered the different level of blue-enriched light